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Chapter 9 : Antibiotic Resistance by Efflux Pumps

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Abstract:

Active efflux can be clinically relevant for β-lactam antibiotics, macrolides, the pristinamycin peptides, fluoroquinolones, and most classically the tetracyclines. From bioinformatic analysis four protein families of efflux pumps that can function in antibiotic resistance have been described. The pumps driven by proton motive force (ΔpH) are categorized in the major facilitator subfamily (MFS), the small multidrug regulator (SMR) family, or the RND (resistance/nodulation/ cell division) family, based on projected size and the need for partner proteins and subunits. A significant breakthrough in understanding the architecture of an ABC type transporter has been obtained by crystallization of the MsbA protein from , at a relatively low resolution, but sufficient to reveal orientation of nucleotide binding domains (NBDs) to transmembrane domains (TMDs) and allowing a model for transporter action. MsbA is homologous to human MDR-1 and mouse MDR3, multidrug resistance transporters that are thought to act physiologically as lipid and phospholipid ‘‘flippases,’’ moving phospholipid molecules from the inner to the outer layer of the membrane bilayer. O157:H7 exhibits resistance to streptomycin, tetracycline, and sulfa drugs and may do so through reduction of outer membrane permeability for uptake.

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9

Key Concept Ranking

Bacterial Proteins
0.9347005
Efflux Pumps
0.54854554
Bacterial Toxins
0.52803296
0.9347005
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Figures

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Untitled

Resistance by action of H and ATP-coupled efflux pumps in bacterial membranes.

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.2
Figure 9.2

Predicted orientation of MFS pumps in the bacterial cytoplasmic membrane. (From Paulsen et al. [1996], with permission.)

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.1
Figure 9.1

Four protein subfamilies of proton-dependent efflux pumps and the ATPase family of efflux pump in antibiotic resistance. (From Paulsen et al. [1996], with permission.)

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.3
Figure 9.3

The maltose transport system: architecture of the MalK dimer. (From Diederichs et al. [2000], with permission.)

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.4
Figure 9.4

Schematic of an ABC transporter. (A) The MsbA dimer and its orientation towards membrane bilayer leaflets. (B) Schematic of lipid A transport by MsbA. (From Chang and Roth [2001], with permission.)

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.5
Figure 9.5

Operon organization of three-component Mex efflux pumps in and operon.

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.6
Figure 9.6

(Left) The architecture of TolC; (Right) models for TolC closed and open states. (Modified from Koronakis et al. [2000], with permission.)

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.7
Figure 9.7

Structural basis of relief of repression of transcription when Mg-tetracycline binds to TetR. (From Orth et al. [2000], with permission.)

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.8
Figure 9.8

Regulatory circuit logic for efflux pump genes.

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.9
Figure 9.9

Binding of lipophilic cation trimethylphosphonium ion to the BmrR repressor. (From Zheleznova et al. [1999], with permission.)

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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Image of Figure 9.10
Figure 9.10

Culture of O157:H7. (Courtesy of D. E. Graham.)

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9
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References

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Tables

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Table 9.1

Summary of reported drug resistance profiles for multidrug-resistance-inducing efflux pumps (modified from Putman et al. [2000])

Citation: Walsh C. 2003. Antibiotic Resistance by Efflux Pumps, p 124-140. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch9

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